Despite the unheralded success of immune checkpoint blockade in delivering durable responses for some patients with non-small-cell lung cancer (NSCLC), the majority of patients do not respond. PD-L1 tumour expression and pre-existing tumour T-cell infiltration have been correlated with improved clinical outcomes to anti-PD-1/anti-PD-L1. However, patients with tumours that are negative for PD-L1 expression can also respond to treatment. Strategies to combine other treatment modalities like radiotherapy (RT) with immune checkpoint inhibitors are being investigated as means of improving the response rates to PD-1/PD-L1 antibody blockade. RT induces immunogenic changes in cancer cells, can adaptively upregulate tumour cell PD-L1 expression and can improve the efficacy of anti-PD-1/anti-PD-L1 therapy. How we design future clinical trials in NSCLC also depends on practical considerations of delivering these treatment combinations, such as RT dose, fractionation and field volume, as well as scheduling with immune checkpoint blockade. Here, we review reasons for resistance to anti-PD-1/anti-PD-L1 and how RT may be utilised in combination with these drugs to enhance their effect by building better translational research platforms.

中文翻译：

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肺癌的放射治疗和抗 PD-1/PD-L1 组合：建立更好的转化研究平台。


尽管免疫检查点阻断在为一些非小细胞肺癌（NSCLC）患者提供持久反应方面取得了意想不到的成功，但大多数患者没有反应。 PD-L1 肿瘤表达和预先存在的肿瘤 T 细胞浸润与抗 PD-1/抗 PD-L1 临床结果的改善相关。然而，PD-L1 表达阴性的肿瘤患者也可以对治疗产生反应。正在研究将放射治疗 (RT) 等其他治疗方式与免疫检查点抑制剂相结合的策略，作为提高 PD-1/PD-L1 抗体阻断反应率的手段。 RT诱导癌细胞的免疫原性变化，可以适应性上调肿瘤细胞PD-L1的表达，并可以提高抗PD-1/抗PD-L1治疗的疗效。我们如何设计未来的 NSCLC 临床试验还取决于提供这些治疗组合的实际考虑，例如 RT 剂量、分割和视野体积，以及免疫检查点封锁的安排。在此，我们回顾了抗 PD-1/抗 PD-L1 耐药的原因，以及如何将 RT 与这些药物联合使用，通过建立更好的转化研究平台来增强其疗效。